Translational Shifts in Preclinical Models of Depression: Implications for Biomarkers for Improved Treatments

  • Chloe Slaney
  • Justyna K. Hinchcliffe
  • Emma S. J. RobinsonEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 40)


Understanding the neurobiology of major depressive disorder (MDD) remains one of the major challenges in neuroscience. The disease is heterogeneous in nature, and patients present with a varied symptom profile. Studies seeking to identify biomarkers for MDD diagnosis and treatment have not yet found any one candidate which achieves sufficient sensitivity and specificity. In this article, we consider whether neuropsychological impairments, specifically affective biases, could provide a behavioural biomarker. Affective biases are observed when emotional states influence cognitive function. These biases have been shown to influence a number of different cognitive domains with some specific deficits observed in MDD. It has also been possible to use these neuropsychological tests to inform the development of translational tasks for non-human species. The results from studies in rodents suggest that quantification of affective biases is feasible and may provide a reliable method to predict antidepressant efficacy as well as pro-depressant risk. Animal studies suggest that affective state-induced biases in learning and memory operate over a different time course to biases influencing decision-making. The implications for these differences in terms of task validity and future ideas relating to affective biases and MDD are discussed. We also describe our most recent studies which have shown that depression-like phenotypes share a common deficit in reward-related learning and memory which we refer to as a reward-induced positive bias. This deficit is dissociable from more typical measures of hedonic behaviour and motivation for reward and may represent an important and distinct form of reward deficit linked to MDD.


Affective bias Animal model Antidepressant Predictive validity Pro-depressant Reward 



ESJR currently has research funding from the MRC, BBSRC, Wellcome Trust and academic research grants from Boehringer Ingelheim and Eli Lilly. She has also previously received research funding from MSD, Pfizer and GSK. Previous support which has contributed to the development of this work includes funding from RCUK and the British Pharmacological Society Integrative Pharmacology Fund. CS is funded by a Wellcome Trust doctoral training studentship. JKH is funded by a University of Bristol PhD Studentship.


  1. Amsterdam JD, Settle RG, Doty RL, Abelman E, Winokur A (1987) Taste and smell perception in depression. Biol Psychiatry 22(12):1481–1485PubMedGoogle Scholar
  2. Anderson MH, Hardcastle C, Munafò MR, Robinson ES (2012) Evaluation of a novel translational task for assessing emotional biases in different species. Cogn Affect Behav Neurosci 12(2):373–381PubMedGoogle Scholar
  3. Anderson MH, Munafo MR, Robinson ES (2013) Investigating the psychopharmacology of cognitive affective bias in rats using an affective tone discrimination task. Psychopharmacology (Berl) 226(3):601–613Google Scholar
  4. Anderson MH et al (2015) Evaluation of a novel translational task for assessing emotional biases in different species.
  5. Aylward J, Hales C, Robinson E, Robinson OJ (2017) Back-translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders. bioRxiv:143453Google Scholar
  6. Bari A, Theobald DE, Caprioli D, Mar AC, Aidoo-Micah A, Dalley JW, Robbins TW (2010) Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats. Neuropsychopharmacology 35(6):1290–1301PubMedPubMedCentralGoogle Scholar
  7. Beck AT (1967) Depression: clinical, experimental, and theoretical aspects. Hoeber Medical Division, New York, NYGoogle Scholar
  8. Beck AT, Steer RA, Brown GK (1996) Beck depression inventory-II. Psychological Corporation, San Antonio, TX, pp 12–15Google Scholar
  9. Berlin I, Givry-Steiner L, Lecrubier Y, Puech AJ (1998) Measures of anhedonia and hedonic responses to sucrose in depressive and schizophrenic patients in comparison with healthy subjects. Eur Psychiatry 13(6):303–309PubMedGoogle Scholar
  10. Berton O, Hahn CG, Thase ME (2012) Are we getting closer to valid translational models for major depression? Science 338(6103):75–79PubMedGoogle Scholar
  11. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69(3):89–95Google Scholar
  12. Bourke C, Douglas K, Porter R (2010) Processing of facial emotion expression in major depression: a review. Aust N Z J Psychiatry 44(8):681–696PubMedGoogle Scholar
  13. Brittlebank AD, Scott J, Williams JM, Ferrier IN (1993) Autobiographical memory in depression: state or trait marker? Br J Psychiatry 162:118–121PubMedGoogle Scholar
  14. Caseras X, Garner M, Bradley BP, Mogg K (2007) Biases in visual orienting to negative and positive scenes in dysphoria: an eye movement study. J Abnorm Psychol 116(3):491–497PubMedGoogle Scholar
  15. Clark L, Chamberlain SR, Sahakian BJ (2009) Neurocognitive mechanisms in depression: implications for treatment. Annu Rev Neurosci 32:57–74PubMedGoogle Scholar
  16. Coles ME, Heimberg RG (2002) Memory biases in the anxiety disorders: current status. Clin Psychol Rev 22(4):587–627PubMedGoogle Scholar
  17. Commons KG, Cholanians AB, Babb JA, Ehlinger DG (2017) The rodent forced swim test measures stress-coping strategy, not depression-like behavior. ACS Chem Neurosci 8(5):955–960PubMedPubMedCentralGoogle Scholar
  18. Cryan JF, Slattery DA (2007) Animal models of mood disorders: recent developments. Curr Opin Psychiatry 20(1):1–7PubMedGoogle Scholar
  19. Cuthbert BN, Insel TR (2013) Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med 11:126PubMedPubMedCentralGoogle Scholar
  20. de Kloet ER, Molendijk ML (2016) Coping with the forced swim stressor: towards understanding an adaptive mechanism. Neural Plast 2016:6503162PubMedPubMedCentralGoogle Scholar
  21. Der-Avakian A, D’Souza MS, Pizzagalli DA, Markou A (2013) Assessment of reward responsiveness in the response bias probabilistic reward task in rats: implications for cross-species translational research. Transl Psychiatry 3:e297PubMedPubMedCentralGoogle Scholar
  22. Der-Avakian A, Barnes SA, Markou A, Pizzagalli DA (2016) Translational assessment of reward and motivational deficits in psychiatric disorders. Curr Top Behav Neurosci 28:231–262PubMedPubMedCentralGoogle Scholar
  23. Der-Avakian A, D’Souza MS, Potter DN, Chartoff EH, Carlezon WA Jr, Pizzagalli DA, Markou A (2017) Social defeat disrupts reward learning and potentiates striatal nociceptin/orphanin FQ mRNA in rats. Psychopharmacology (Berl) 234(9–10):1603–1614Google Scholar
  24. Dichter GS, Smoski MJ, Kampov-Polevoy AB, Gallop R, Garbutt JC (2010) Unipolar depression does not moderate responses to the sweet taste test. Depress Anxiety 27(9):859–863PubMedPubMedCentralGoogle Scholar
  25. DSM-V (2013) DSM-5 task force. Diagnostic and statistical manual of mental disorders: DSM-5, 5th edn. American Psychiatric Association, Washington, DCGoogle Scholar
  26. Elliott R, Zahn R, Deakin JF, Anderson IM (2011) Affective cognition and its disruption in mood disorders. Neuropsychopharmacology 36(1):153–182PubMedGoogle Scholar
  27. Enkel T et al (2009) Ambiguous-cue interpretation is biased under stress- and depression-like states in rats.
  28. Geyer MAMA (1995) Animal models of psychiatric disorders. In: Bloom FE, Kupfer DJ (eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York, NY, pp 787–798Google Scholar
  29. Gotlib IH, Joormann J (2010) Cognition and depression: current status and future directions. Annu Rev Clin Psychol 6(1):285–312PubMedPubMedCentralGoogle Scholar
  30. Gur RC, Erwin RJ, Gur RE, Zwil AS, Heimberg C, Kraemer HC (1992) Facial emotion discrimination: II. Behavioral findings in depression. Psychiatry Res 42(3):241–251PubMedGoogle Scholar
  31. Hales CA, Stuart SA, Anderson MH, Robinson ES (2014) Modelling cognitive affective biases in major depressive disorder using rodents. Br J Pharmacol 171(20):4524–4538PubMedPubMedCentralGoogle Scholar
  32. Hales CA, Robinson ES, Houghton CJ (2016) Diffusion modelling reveals the decision making processes underlying negative judgement bias in rats. PLoS One 11(3):e0152592PubMedPubMedCentralGoogle Scholar
  33. Hales CA, Houghton CJ, Robinson ESJ (2017) Behavioural and computational methods reveal differential effects for how delayed and rapid onset antidepressants effect decision making in rats. Eur Neuropsychopharmacol 27(12):1268–1280PubMedPubMedCentralGoogle Scholar
  34. Hamilton MAX (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55PubMedGoogle Scholar
  35. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62PubMedPubMedCentralGoogle Scholar
  36. Harding EJ, Paul ES, Mendl M (2004) Animal behaviour: cognitive bias and affective state. Nature 427(6972):312PubMedGoogle Scholar
  37. Harmer C, Goodwin G, Cowen P (2009a) Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. Br J Psychiatry 195(2):102–108PubMedGoogle Scholar
  38. Harmer CJ, O’Sullivan U, Favaron E, Massey-Chase R, Ayres R, Reinecke A, Goodwin GM, Cowen PJ (2009b) Effect of acute antidepressant administration on negative affective bias in depressed patients. Am J Psychiatr 166(10):1178–1184PubMedGoogle Scholar
  39. Harmer CJ, Duman RS, Cowen PJ (2017) How do antidepressants work? New perspectives for refining future treatment approaches. Lancet Psychiatry 4(5):409–418PubMedPubMedCentralGoogle Scholar
  40. Hasler G, Drevets WC, Manji HK, Charney DS (2004) Discovering endophenotypes for major depression. Neuropsychopharmacology 29(10):1765–1781PubMedGoogle Scholar
  41. Hinchcliffe JK, Stuart SA, Mendl M, Robinson ESJ (2017) Further validation of the affective bias test for predicting antidepressant and pro-depressant risk: effects of pharmacological and social manipulations in male and female rats. Psychopharmacology (Berl) 234(20):3105–3116Google Scholar
  42. Hirschfeld RM (2000) History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 61(suppl 6):4–6PubMedGoogle Scholar
  43. Insel TR (2014) The NIMH research domain criteria (RDoC) project: precision medicine for psychiatry. Am J Psychiatry 171(4):395–397Google Scholar
  44. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P (2010) Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 167(7):748–751Google Scholar
  45. Jentsch MC, Van Buel EM, Bosker FJ, Gladkevich AV, Klein HC, Oude Voshaar RC, Ruhe EG, Eisel UL, Schoevers RA (2015) Biomarker approaches in major depressive disorder evaluated in the context of current hypotheses. Biomark Med 9(3):277–297PubMedGoogle Scholar
  46. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095–3105PubMedGoogle Scholar
  47. Klein AM, de Voogd L, Wiers RW, Salemink E (2017) Biases in attention and interpretation in adolescents with varying levels of anxiety and depression. Cogn Emot:1–9Google Scholar
  48. Kregiel J (2016) Anandamide mediates cognitive judgement bias in rats.
  49. Lépine J-P, Briley M (2011) The increasing burden of depression. Neuropsychiatr Dis Treat 7(suppl 1):3–7PubMedPubMedCentralGoogle Scholar
  50. Leppänen JM (2006) Emotional information processing in mood disorders: a review of behavioral and neuroimaging findings. Curr Opin Psychiatry 19(1):34–39PubMedGoogle Scholar
  51. Marchetti I, Everaert J, Dainer-Best J, Loeys T, Beevers CG, Koster EHW (2018) Specificity and overlap of attention and memory biases in depression. J Affect Disord 225:404–412PubMedGoogle Scholar
  52. Mathews A, MacLeod C (2005) Cognitive vulnerability to emotional disorders. Annu Rev Clin Psychol 1(1):167–195Google Scholar
  53. Matt GE, Vázquez C, Campbell WK (1992) Mood-congruent recall of affectively toned stimuli: a meta-analytic review. Clin Psychol Rev 12(2):227–255Google Scholar
  54. McCabe C, Woffindale C, Harmer CJ, Cowen PJ (2012) Neural processing of reward and punishment in young people at increased familial risk of depression. Biol Psychiatry 72(7):588–594PubMedGoogle Scholar
  55. McFarland BR, Klein DN (2009) Emotional reactivity in depression: diminished responsiveness to anticipated reward but not to anticipated punishment or to nonreward or avoidance. Depress Anxiety 26(2):117–122PubMedGoogle Scholar
  56. Mogg K, Bradley BP (2005) Attentional bias in generalized anxiety disorder versus depressive disorder. Cogn Ther Res 29(1):29–45Google Scholar
  57. Murphy S, Norbury R, O’Sullivan U, Cowen P, Harmer C (2009) Effect of a single dose of citalopram on amygdala response to emotional faces. Br J Psychiatry 194(6):535–540PubMedPubMedCentralGoogle Scholar
  58. Neill JC, Harte MK, Haddad PM, Lydall ES, Dwyer DM (2014) Acute and chronic effects of NMDA receptor antagonists in rodents, relevance to negative symptoms of schizophrenia: a translational link to humans. Eur Neuropsychopharmacol 24(5):822–835PubMedGoogle Scholar
  59. Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13(10):1161–1169PubMedPubMedCentralGoogle Scholar
  60. Neumann ID, Wegener G, Homberg JR, Cohen H, Slattery DA, Zohar J, Olivier JD, Mathe AA (2011) Animal models of depression and anxiety: what do they tell us about human condition? Prog Neuropsychopharmacol Biol Psychiatry 35(6):1357–1375PubMedGoogle Scholar
  61. Nusslock R, Alloy LB (2017) Reward processing and mood-related symptoms: an RDoC and translational neuroscience perspective. J Affect Disord 216:3–16PubMedGoogle Scholar
  62. Papciak J, Popik P, Fuchs E, Rygula R (2013) Chronic psychosocial stress makes rats more ‘pessimistic’ in the ambiguous-cue interpretation paradigm. Behav Brain Res 256:305–310PubMedGoogle Scholar
  63. Paul ES, Harding EJ, Mendl M (2005) Measuring emotional processes in animals: the utility of a cognitive approach. Neurosci Biobehav Rev 29(3):469–491PubMedGoogle Scholar
  64. Pechtel P, Dutra SJ, Goetz EL, Pizzagalli DA (2013) Blunted reward responsiveness in remitted depression. J Psychiatr Res 47(12):1864–1869PubMedPubMedCentralGoogle Scholar
  65. Pizzagalli DA, Jahn AL, O’Shea JP (2005) Toward an objective characterization of an anhedonic phenotype: a signal-detection approach. Biol Psychiatry 57(4):319–327PubMedPubMedCentralGoogle Scholar
  66. Pizzagalli DA, Iosifescu D, Hallett LA, Ratner KG, Fava M (2008) Reduced hedonic capacity in major depressive disorder: evidence from a probabilistic reward task. J Psychiatr Res 43(1):76–87PubMedPubMedCentralGoogle Scholar
  67. Porsolt RD, Le Pichon M, Jalfre M (1977) Depression: a new animal model sensitive to antidepressant treatments. Nature 266(5604):730–732PubMedPubMedCentralGoogle Scholar
  68. Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47(4):379–391Google Scholar
  69. Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M (1979) Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 57(2–3):201–210PubMedGoogle Scholar
  70. Pringle A, Browning M, Cowen PJ, Harmer CJ (2011) A cognitive neuropsychological model of antidepressant drug action. Prog Neuropsychopharmacol Biol Psychiatry 35(7):1586–1592PubMedGoogle Scholar
  71. Refsgaard LK, Haubro K, Pickering DS, Stuart SA, Robinson ES, Andreasen JT (2016) Effects of sertraline, duloxetine, vortioxetine, and idazoxan in the rat affective bias test. Psychopharmacology (Berl) 233(21–22):3763–3770Google Scholar
  72. Ressler KJ, Mayberg HS (2007) Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci 10(9):1116–1124PubMedPubMedCentralGoogle Scholar
  73. Rinck M, Becker ES (2005) A comparison of attentional biases and memory biases in women with social phobia and major depression. J Abnorm Psychol 114(1):62–74PubMedGoogle Scholar
  74. Robinson ES, Roiser JP (2016) Affective biases in humans and animals. Curr Top Behav Neurosci 28:263–286PubMedGoogle Scholar
  75. Roiser JP, Elliott R, Sahakian BJ (2012a) Cognitive mechanisms of treatment in depression. Neuropsychopharmacology 37(1):117–136PubMedGoogle Scholar
  76. Roiser JP, Levy J, Fromm SJ, Goldman D, Hodgkinson CA, Hasler G, Sahakian BJ, Drevets WC (2012b) Serotonin transporter genotype differentially modulates neural responses to emotional words following tryptophan depletion in patients recovered from depression and healthy volunteers. J Psychopharmacol 26(11):1434–1442PubMedPubMedCentralGoogle Scholar
  77. Romer Thomsen K, Whybrow PC, Kringelbach ML (2015) Reconceptualizing anhedonia: novel perspectives on balancing the pleasure networks in the human brain. Front Behav Neurosci 9:49PubMedPubMedCentralGoogle Scholar
  78. Ruhé HG, Mason NS, Schene AH (2007) Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry 12(4):331–359PubMedGoogle Scholar
  79. Rygula R (2015) Acute administration of lithium, but not valproate, modulates cognitive judgement bias in rats.
  80. Rygula R, Abumaria N, Flugge G, Fuchs E, Ruther E, Havemann-Reinecke U (2005) Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 162(1):127–134PubMedGoogle Scholar
  81. Rygula R, Papciak J, Popik P (2014a) The effects of acute pharmacological stimulation of the 5-HT, NA and DA systems on the cognitive judgement bias of rats in the ambiguous-cue interpretation paradigm. Eur Neuropsychopharmacol 24(7):1103–1111PubMedGoogle Scholar
  82. Rygula R, Szczech E, Papciak J, Nikiforuk A, Popik P (2014b) The effects of cocaine and mazindol on the cognitive judgement bias of rats in the ambiguous-cue interpretation paradigm. Behav Brain Res 270:206–212PubMedGoogle Scholar
  83. Sahin C, Doostdar N, Neill JC (2016) Towards the development of improved tests for negative symptoms of schizophrenia in a validated animal model. Behav Brain Res 312:93–101PubMedGoogle Scholar
  84. Salem T, Winer ES, Nadorff MR (2017) Combined behavioural markers of cognitive biases are associated with anhedonia. Cogn Emot 31:1–9Google Scholar
  85. Schildkraut JJ (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 122(5):509–522PubMedGoogle Scholar
  86. Scinska A, Sienkiewicz-Jarosz H, Kuran W, Ryglewicz D, Rogowski A, Wrobel E, Korkosz A, Kukwa A, Kostowski W, Bienkowski P (2004) Depressive symptoms and taste reactivity in humans. Physiol Behav 82(5):899–904PubMedGoogle Scholar
  87. Slattery DA, Cryan JF (2014) The ups and downs of modelling mood disorders in rodents. ILAR J 55(2):297–309PubMedGoogle Scholar
  88. Slattery DA, Cryan JF (2017) Modelling depression in animals: at the interface of reward and stress pathways. Psychopharmacology (Berl) 234(9–10):1451–1465Google Scholar
  89. Slattery DA, Markou A, Cryan JF (2007) Evaluation of reward processes in an animal model of depression. Psychopharmacology (Berl) 190(4):555–568Google Scholar
  90. Stahl SM (1998) Mechanism of action of serotonin selective reuptake inhibitors. Serotonin receptors and pathways mediate therapeutic effects and side effects. J Affect Disord 51(3):215–235PubMedGoogle Scholar
  91. Steru L, Chermat R, Thierry B, Simon P (1985) The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology (Berl) 85(3):367–370Google Scholar
  92. Strauss GP, Gold JM (2012) A new perspective on anhedonia in schizophrenia. Am J Psychiatry 169(4):364–373PubMedPubMedCentralGoogle Scholar
  93. Strawbridge R, Young AH, Cleare AJ (2017) Biomarkers for depression: recent insights, current challenges and future prospects. Neuropsychiatr Dis Treat 13:1245–1262PubMedPubMedCentralGoogle Scholar
  94. Stuart SA, Butler P, Munafo MR, Nutt DJ, Robinson ES (2013) A translational rodent assay of affective biases in depression and antidepressant therapy. Neuropsychopharmacology 38(9):1625–1635PubMedPubMedCentralGoogle Scholar
  95. Stuart SA, Butler P, Robinson ES (2014) Animals models of risk factors for suicidal ideation and behaviour. Springer, ChamGoogle Scholar
  96. Stuart SA, Butler P, Munafò MR, Nutt DJ, Robinson ES (2015) Distinct neuropsychological mechanisms may explain delayed- versus rapid-onset antidepressant efficacy. Neuropsychopharmacology 40(9):2165–2174PubMedPubMedCentralGoogle Scholar
  97. Stuart SA, Wood CM, Robinson ESJ (2017) Using the affective bias test to predict drug-induced negative affect: implications for drug safety. Br J Pharmacol 174(19):3200–3210PubMedPubMedCentralGoogle Scholar
  98. Surguladze SA, Young AW, Senior C, Brébion G, Travis MJ, Phillips ML (2004) Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Neuropsychology 18(2):212–218PubMedGoogle Scholar
  99. Swiecicki L, Zatorski P, Bzinkowska D, Sienkiewicz-Jarosz H, Szyndler J, Scinska A (2009) Gustatory and olfactory function in patients with unipolar and bipolar depression. Prog Neuropsychopharmacol Biol Psychiatry 33(5):827–834PubMedGoogle Scholar
  100. Thomsen KR (2015) Measuring anhedonia: impaired ability to pursue, experience, and learn about reward. Front Psychol 6:1409PubMedPubMedCentralGoogle Scholar
  101. Tranter R, Bell D, Gutting P, Harmer C, Healy D, Anderson IM (2009) The effect of serotonergic and noradrenergic antidepressants on face emotion processing in depressed patients. J Affect Disord 118(1–3):87–93PubMedGoogle Scholar
  102. Treadway MT, Zald DH (2011) Reconsidering anhedonia in depression: lessons from translational neuroscience. Neurosci Biobehav Rev 35(3):537–555PubMedGoogle Scholar
  103. Treadway MT, Zald DH (2013) Parsing anhedonia: translational models of reward-processing deficits in psychopathology. Curr Dir Psychol Sci 22(3):244–249PubMedPubMedCentralGoogle Scholar
  104. Uddin M (2014) Blood-based biomarkers in depression: emerging themes in clinical research. Mol Diagn Ther 18(5):469–482PubMedGoogle Scholar
  105. Vardigan JD, Huszar SL, McNaughton CH, Hutson PH, Uslaner JM (2010) MK-801 produces a deficit in sucrose preference that is reversed by clozapine, D-serine, and the metabotropic glutamate 5 receptor positive allosteric modulator CDPPB: relevance to negative symptoms associated with schizophrenia? Pharmacol Biochem Behav 95(2):223–229PubMedGoogle Scholar
  106. Vrieze E, Pizzagalli DA, Demyttenaere K, Hompes T, Sienaert P, de Boer P, Schmidt M, Claes S (2013) Reduced reward learning predicts outcome in major depressive disorder. Biol Psychiatry 73(7):639–645PubMedGoogle Scholar
  107. Watson D, Naragon-Gainey K (2010) On the specificity of positive emotional dysfunction in psychopathology: evidence from the mood and anxiety disorders and schizophrenia/schizotypy. Clin Psychol Rev 30(7):839–848PubMedGoogle Scholar
  108. Whitton AE, Treadway MT, Pizzagalli DA (2015) Reward processing dysfunction in major depression, bipolar disorder and schizophrenia. Curr Opin Psychiatry 28(1):7–12PubMedPubMedCentralGoogle Scholar
  109. Williams JM, Scott J (1988) Autobiographical memory in depression. Psychol Med 18(3):689–695PubMedGoogle Scholar
  110. Williams JM, Barnhofer T, Crane C, Herman D, Raes F, Watkins E, Dalgleish T (2007) Autobiographical memory specificity and emotional disorder. Psychol Bull 133(1):122–148PubMedPubMedCentralGoogle Scholar
  111. Willner P (1995) Animal models of depression: validity and applications. Adv Biochem Psychopharmacol 49:19–41PubMedGoogle Scholar
  112. Willner P (2005) Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 52(2):90–110Google Scholar
  113. Willner P, Mitchell PJ (2002) The validity of animal models of predisposition to depression. Behav Pharmacol 13(3):169–188PubMedGoogle Scholar
  114. Willner P, Towell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl) 93(3):358–364Google Scholar
  115. Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21(9):655–679PubMedPubMedCentralGoogle Scholar
  116. World Health Organization (1992) The ICD-10 classification of mental and behavioural disorders : clinical descriptions and diagnostic guidelines. World Health Organization, GenevaGoogle Scholar
  117. Zacharko RM, Anisman H (1991) Stressor-induced anhedonia in the mesocorticolimbic system. Neurosci Biobehav Rev 15(3):391–405PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Chloe Slaney
    • 1
  • Justyna K. Hinchcliffe
    • 1
  • Emma S. J. Robinson
    • 1
    Email author
  1. 1.School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences BuildingUniversity WalkBristolUK

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